Nonalcoholic steatohepatitis in children: A multicenter clinicopathological study
Nonalcoholic fatty liver disease (NAFLD) may have distinct histological features in children and adults, but to date limited data are available on the spectrum and significance of histological lesions in pediatric patients. We conducted a multicenter study of children with well‐characterized, biopsy...
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Published in | Hepatology (Baltimore, Md.) Vol. 50; no. 4; pp. 1113 - 1120 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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01.10.2009
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Abstract | Nonalcoholic fatty liver disease (NAFLD) may have distinct histological features in children and adults, but to date limited data are available on the spectrum and significance of histological lesions in pediatric patients. We conducted a multicenter study of children with well‐characterized, biopsy‐proven NAFLD to (1) assess the presence and significance of a constellation of histological lesions and (2) identify clinical and laboratory predictors of disease severity. One hundred thirty children with NAFLD seen from 1995 to 2007 in five centers in the United States and Canada were studied. Clinical and laboratory data were collected. Slides stained with hematoxylin‐eosin and trichrome were evaluated by two liver pathologists. The NAFLD activity score (NAS) and the pattern of liver injury (type 1 or adult versus type 2 or pediatric nonalcoholic steatohepatitis [NASH]) were recorded. Fibrosis was staged using a published 7‐point scale. The median age was 12 years (range, 4‐18 years); 63% were boys, and 52% were Caucasian. Fibrosis was present in 87% of patients; of these, stage 3 (bridging fibrosis) was present in 20%. No patient had cirrhosis. The median NAS was 4. Overlapping features of both type 1 (adult pattern) and type 2 (pediatric pattern) NASH were found in 82% of patients. Compared with patients with no or mild fibrosis, those with significant fibrosis were more likely to have higher lobular and portal inflammation scores (P < 0.01), perisinusoidal fibrosis (P < 0.001), and NAS ≥5 (P < 0.005). Serum aspartate aminotransferase levels were the only clinical or laboratory data that independently predicted severity of fibrosis (P = 0.003). Conclusion: Our results highlight the limitations of published proposals to classify pediatric NAFLD, and identified histological lesions associated with progressive disease. (HEPATOLOGY 2009.) |
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AbstractList | Nonalcoholic fatty liver disease (NAFLD) may have distinct histological features in children and adults, but to date limited data are available on the spectrum and significance of histological lesions in pediatric patients. We conducted a multicenter study of children with well-characterized, biopsy-proven NAFLD to (1) assess the presence and significance of a constellation of histological lesions and (2) identify clinical and laboratory predictors of disease severity. One hundred thirty children with NAFLD seen from 1995 to 2007 in five centers in the United States and Canada were studied. Clinical and laboratory data were collected. Slides stained with hematoxylin-eosin and trichrome were evaluated by two liver pathologists. The NAFLD activity score (NAS) and the pattern of liver injury (type 1 or adult versus type 2 or pediatric nonalcoholic steatohepatitis [NASH]) were recorded. Fibrosis was staged using a published 7-point scale. The median age was 12 years (range, 4-18 years); 63% were boys, and 52% were Caucasian. Fibrosis was present in 87% of patients; of these, stage 3 (bridging fibrosis) was present in 20%. No patient had cirrhosis. The median NAS was 4. Overlapping features of both type 1 (adult pattern) and type 2 (pediatric pattern) NASH were found in 82% of patients. Compared with patients with no or mild fibrosis, those with significant fibrosis were more likely to have higher lobular and portal inflammation scores (P < 0.01), perisinusoidal fibrosis (P < 0.001), and NAS > or =5 (P < 0.005). Serum aspartate aminotransferase levels were the only clinical or laboratory data that independently predicted severity of fibrosis (P = 0.003).
Our results highlight the limitations of published proposals to classify pediatric NAFLD, and identified histological lesions associated with progressive disease. Nonalcoholic fatty liver disease (NAFLD) may have distinct histological features in children and adults, but to date limited data are available on the spectrum and significance of histological lesions in pediatric patients. We conducted a multicenter study of children with well-characterized, biopsy-proven NAFLD to (1) assess the presence and significance of a constellation of histological lesions and (2) identify clinical and laboratory predictors of disease severity. One hundred thirty children with NAFLD seen from 1995 to 2007 in five centers in the United States and Canada were studied. Clinical and laboratory data were collected. Slides stained with hematoxylin-eosin and trichrome were evaluated by two liver pathologists. The NAFLD activity score (NAS) and the pattern of liver injury (type 1 or adult versus type 2 or pediatric nonalcoholic steatohepatitis [NASH]) were recorded. Fibrosis was staged using a published 7-point scale. The median age was 12 years (range, 4-18 years); 63% were boys, and 52% were Caucasian. Fibrosis was present in 87% of patients; of these, stage 3 (bridging fibrosis) was present in 20%. No patient had cirrhosis. The median NAS was 4. Overlapping features of both type 1 (adult pattern) and type 2 (pediatric pattern) NASH were found in 82% of patients. Compared with patients with no or mild fibrosis, those with significant fibrosis were more likely to have higher lobular and portal inflammation scores ( P < 0.01), perisinusoidal fibrosis ( P < 0.001), and NAS ≥5 ( P < 0.005). Serum aspartate aminotransferase levels were the only clinical or laboratory data that independently predicted severity of fibrosis ( P = 0.003). UNLABELLEDNonalcoholic fatty liver disease (NAFLD) may have distinct histological features in children and adults, but to date limited data are available on the spectrum and significance of histological lesions in pediatric patients. We conducted a multicenter study of children with well-characterized, biopsy-proven NAFLD to (1) assess the presence and significance of a constellation of histological lesions and (2) identify clinical and laboratory predictors of disease severity. One hundred thirty children with NAFLD seen from 1995 to 2007 in five centers in the United States and Canada were studied. Clinical and laboratory data were collected. Slides stained with hematoxylin-eosin and trichrome were evaluated by two liver pathologists. The NAFLD activity score (NAS) and the pattern of liver injury (type 1 or adult versus type 2 or pediatric nonalcoholic steatohepatitis [NASH]) were recorded. Fibrosis was staged using a published 7-point scale. The median age was 12 years (range, 4-18 years); 63% were boys, and 52% were Caucasian. Fibrosis was present in 87% of patients; of these, stage 3 (bridging fibrosis) was present in 20%. No patient had cirrhosis. The median NAS was 4. Overlapping features of both type 1 (adult pattern) and type 2 (pediatric pattern) NASH were found in 82% of patients. Compared with patients with no or mild fibrosis, those with significant fibrosis were more likely to have higher lobular and portal inflammation scores (P < 0.01), perisinusoidal fibrosis (P < 0.001), and NAS > or =5 (P < 0.005). Serum aspartate aminotransferase levels were the only clinical or laboratory data that independently predicted severity of fibrosis (P = 0.003). CONCLUSIONOur results highlight the limitations of published proposals to classify pediatric NAFLD, and identified histological lesions associated with progressive disease. Nonalcoholic fatty liver disease (NAFLD) may have distinct histological features in children and adults, but to date limited data are available on the spectrum and significance of histological lesions in pediatric patients. We conducted a multicenter study of children with well‐characterized, biopsy‐proven NAFLD to (1) assess the presence and significance of a constellation of histological lesions and (2) identify clinical and laboratory predictors of disease severity. One hundred thirty children with NAFLD seen from 1995 to 2007 in five centers in the United States and Canada were studied. Clinical and laboratory data were collected. Slides stained with hematoxylin‐eosin and trichrome were evaluated by two liver pathologists. The NAFLD activity score (NAS) and the pattern of liver injury (type 1 or adult versus type 2 or pediatric nonalcoholic steatohepatitis [NASH]) were recorded. Fibrosis was staged using a published 7‐point scale. The median age was 12 years (range, 4‐18 years); 63% were boys, and 52% were Caucasian. Fibrosis was present in 87% of patients; of these, stage 3 (bridging fibrosis) was present in 20%. No patient had cirrhosis. The median NAS was 4. Overlapping features of both type 1 (adult pattern) and type 2 (pediatric pattern) NASH were found in 82% of patients. Compared with patients with no or mild fibrosis, those with significant fibrosis were more likely to have higher lobular and portal inflammation scores (P < 0.01), perisinusoidal fibrosis (P < 0.001), and NAS ≥5 (P < 0.005). Serum aspartate aminotransferase levels were the only clinical or laboratory data that independently predicted severity of fibrosis (P = 0.003). Conclusion: Our results highlight the limitations of published proposals to classify pediatric NAFLD, and identified histological lesions associated with progressive disease. (HEPATOLOGY 2009.) |
Author | Charatcharoenwitthaya, Phunchai Xanthakos, Stavra A. Whitington, Peter F. Ling, Simon C. Kohli, Rohit Lopez, Rocio Feldstein, Ariel E. Carter‐Kent, Christine Yerian, Lisa M. Yap, Jason Brunt, Elizabeth M. Angulo, Paul McCullough, Arthur J. |
AuthorAffiliation | 7 Division of Gastroenterology and Hepatology, Children's Memorial Hospital, Chicago, IL 8 Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH 3 Department of Pathology and Immunology, Washington University, St. Louis, MO 9 Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 4 Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 2 Department of Pathology, Cleveland Clinic, Cleveland, OH 6 Division of Gastroenterology and Hepatology, The Hospital for Sick Children, Toronto, Ontario, Canada 5 Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 10 Department of Cell Biology, Cleveland Clinic, Cleveland, OH 1 Department of Pediatric Gastroenterology and Nutrition, Cleveland Clinic, Cleveland, OH |
AuthorAffiliation_xml | – name: 2 Department of Pathology, Cleveland Clinic, Cleveland, OH – name: 8 Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH – name: 9 Digestive Disease Institute, Cleveland Clinic, Cleveland, OH – name: 6 Division of Gastroenterology and Hepatology, The Hospital for Sick Children, Toronto, Ontario, Canada – name: 4 Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN – name: 10 Department of Cell Biology, Cleveland Clinic, Cleveland, OH – name: 5 Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH – name: 7 Division of Gastroenterology and Hepatology, Children's Memorial Hospital, Chicago, IL – name: 1 Department of Pediatric Gastroenterology and Nutrition, Cleveland Clinic, Cleveland, OH – name: 3 Department of Pathology and Immunology, Washington University, St. Louis, MO |
Author_xml | – sequence: 1 givenname: Christine surname: Carter‐Kent fullname: Carter‐Kent, Christine – sequence: 2 givenname: Lisa M. surname: Yerian fullname: Yerian, Lisa M. – sequence: 3 givenname: Elizabeth M. surname: Brunt fullname: Brunt, Elizabeth M. – sequence: 4 givenname: Paul surname: Angulo fullname: Angulo, Paul – sequence: 5 givenname: Rohit surname: Kohli fullname: Kohli, Rohit – sequence: 6 givenname: Simon C. surname: Ling fullname: Ling, Simon C. – sequence: 7 givenname: Stavra A. surname: Xanthakos fullname: Xanthakos, Stavra A. – sequence: 8 givenname: Peter F. surname: Whitington fullname: Whitington, Peter F. – sequence: 9 givenname: Phunchai surname: Charatcharoenwitthaya fullname: Charatcharoenwitthaya, Phunchai – sequence: 10 givenname: Jason surname: Yap fullname: Yap, Jason – sequence: 11 givenname: Rocio surname: Lopez fullname: Lopez, Rocio – sequence: 12 givenname: Arthur J. surname: McCullough fullname: McCullough, Arthur J. – sequence: 13 givenname: Ariel E. surname: Feldstein fullname: Feldstein, Ariel E. email: feldsta@ccf.org |
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PublicationYear | 2009 |
Publisher | Wiley Subscription Services, Inc., A Wiley Company Wiley |
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liver disease. publication-title: Mod Pathol doi: 10.1038/modpathol.3800680 contributor: fullname: Brunt |
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SubjectTerms | Adolescent Aspartate Aminotransferases - blood Biological and medical sciences Biopsy Canada Child Child, Preschool Cohort Studies Disease Progression Fatty Liver - blood Fatty Liver - diagnosis Fatty Liver - pathology Female Gastroenterology. Liver. Pancreas. Abdomen Humans Liver - pathology Liver Cirrhosis - pathology Liver. Biliary tract. Portal circulation. Exocrine pancreas Male Medical sciences Predictive Value of Tests Prognosis Retrospective Studies Severity of Illness Index United States |
Title | Nonalcoholic steatohepatitis in children: A multicenter clinicopathological study |
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